Effect of Trehalose on PC12 Cells Overexpressing Wild-Type or A53T Mutant α-synuclein
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Accumulation of α-synuclein (α-Syn) is a common pathology for both familiar and sporadic Parkinson’s disease (PD), enhancing its clearance might be a promising strategy for treating PD. To assess the potential of trehalose in this regard, we investigated its effect on the PC12 cells overexpressing wild type (WT) or A53T mutant α-Syn and the implicated pathway it might mediated. We observed that trehalose promoted the clearance of A53T α-Syn but not WT α-Syn in PC12 cells, and confirmed the increased LC3 and Lysotracker RED positive autolysosomes by using lysotracker and LC3 staining, the enhanced expression of LC3-II in Western blot, and more autophagosomes under Transmission Electron Microscope in a dose dependent manner after the trehalose treatment. The activation of autophagy can be alleviated by applying macroautophagy inhibitor 3-methyladenine (3-MA). In addition, degradation of A53T and WT α-Syn was blocked after Ubiquitin Proteasome System (UPS) inhibitor (MG132) was applied in those PC12 cells overexpressing A53T or WT α-Syn, suggesting that A53T α-Syn could be degraded by both UPS and macroautophagy. But the effect of trehalose on A53T α-Syn is mainly mediated through the macroautophagy pathway, which is not a dominant way for WT α-Syn clearance. Further in vivo research will be needed to verify the effectiveness of trehalose in treating PD.
KeywordsTrehalose α-synuclein Parkinson’s disease Autophagy Macroautophagy Proteasome inhibitor
Ubiquitin Proteasome System
Autophagy Lysosome System
Transmission electron microscope
3-(4,5-dimethylthiazol-2-yl)-2,5-dipheyltetrazolium Bromide assay
This study was supported by the grants (30600663, 81071018) from the Natural Science Foundation of China, Project (10PJ1401700) of Pujiang Talents at Shanghai, project (09411960900) from Science and Technology Commission of Shanghai Municipality, and project (2010-116) of Shanghai Municipal Health Bureau.